Case 21-2004 a 63-Year-Old Man Castration

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Case 21-2004: A 63-Year-Old Man with Metastatic Prostate Carcinoma

Refractory to Hormone Therapy

Donald S. Kaufman, M.D., W. Scott McDougal, M.D., Anthony L. Zietman, M.D., Mukesh G. Harisinghani, M.D., and Robert H. Young, M.D.

From the Division of Medical Oncology, De-partment of Medicine (D.S.K.), and the De-partments of Urology (W.S.M.), RadiationOncology (A.L.Z.), Radiology (M.G.H.), andPathology (R.H.Y.), Massachusetts GeneralHospital; and the Departments of Medi-cine (D.S.K.), Urology (W.S.M.), RadiationOncology (A.L.Z.), Radiology (M.G.H.),and Pathology (R.H.Y.), Harvard MedicalSchool.

N Engl J Med 2004;351:171-8.

Copyright 2004 Massachusetts Medical Society.

A 63-year-old man was evaluated in the clinic because of metastatic prostate cancerthat was no longer responding to hormone therapy.

The patient had been well until eight years before he came to the clinic, when he hadnoticed a decreased urinary stream and urinary hesitancy. A test for prostate-specificantigen (PSA) six months later showed a level of 2.7 ng per milliliter; six months afterthat, the PSA level was 7.7 ng per milliliter. A transrectal needle biopsy of the prostateshowed adenocarcinoma, Gleason grade 3 to 4 (on a scale of 1 to 5, with 1 indicatinglow-grade carcinoma, and 5 high-grade carcinoma), involving all the biopsy cores (Fig.1A and 1B). Computed tomographic (CT) scans of the abdomen and pelvis and a bonescan showed no abnormalities. The general physical examination also showed no ab-normalities. Rectal examination revealed a firm, nodular area, 2 to 3 cm in diameter, thatinvolved the left lobe of the prostate and that appeared to go to the edge of the gland. Theright lobe was diffusely firm. Laboratory studies and chest radiographic studies showedno abnormalities.

Two months later, the patient was taken to the operating room for a radical prostatec-tomy. On intraoperative examination of specimens obtained by bilateral pelvic lymph-node biopsy, involvement by metastatic prostate cancer was grossly evident (Fig. 1C).The procedure was terminated, and the prostatectomy was not performed. After theoperation, the patients disease was staged as T2N2M0 (a tumor that is palpable or vis-ible on ultrasound, involves both lobes, is associated with more than one positive region-al lymph node, and is not accompanied by distant metastases). He was discharged, andtreatment with flutamide at a dose of 250 mg three times daily was prescribed. Twomonths later, the patients PSA level was 1.1 ng per milliliter. External-beam radiationtreatments were administered, with a total dose of 69.4 Gy, and were completed sixmonths after the initial diagnosis.

At that time, the patients PSA level was 0.5 ng per milliliter, and it remained at or be-low that level for the next six years while he continued taking flutamide. Magnetic res-onance imaging (MRI) of the lumbar spine that was performed four years after the diag-nosis showed no abnormalities, and the results of all liver-function tests were normal.

presentation of case

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Five and a half years after the diagnosis, a bone scanshowed no abnormalities. Six years after the diagno-sis, the patients PSA level was 0.2 ng per milliliter.

Eleven months later, the PSA level was 0.9 ngper milliliter; one month after that (seven years af-ter the initial diagnosis), it was 1.4 ng per milliliter.The daily flutamide treatment was discontinued.One month later, a bone scan showed increased up-take at the T11 vertebra, which was suggestive ofmetastatic disease, but an MRI scan showed no ab-normalities. Over the next five months, the patientsPSA level rose to 4.0 and then to 6.6 ng per milliliter.An abdominopelvic CT scan showed newly enlargedretroperitoneal lymph nodes, which were thought torepresent metastatic disease. A bone scan showedno metastatic disease.

One month later, leuprolide by intramuscular in-jection was begun at an initial dose of 7.5 mg, fol-lowed one month later by 22.5 mg, which was thengiven every three months. Four months later, thePSA level was 6.4 ng per milliliter. A bone scan ob-tained one month later showed metastatic diseaseat T10, L5, the right humerus, and the ribs bilater-ally (Fig. 2A). An abdominopelvic CT scan ob-tained the same day showed progression of theretroperitoneal lymphadenopathy and a newly en-

larged lymph node in the right retrocrural area (Fig.3A). A CT scan of the chest showed multiple pulmo-nary nodules and mediastinal and left hilar lymph-adenopathy, which were thought to represent met-astatic disease (Fig. 4A).

Dr. Donald S. Kaufman:

Over a span of eight years, thisman has been cared for by urologists, radiation on-cologists, and medical oncologists, and his care hasincluded prostate biopsies, an exploratory laparoto-my, radiation treatment, and hormone therapy. Eachof these treatment decisions required a riskbenefitanalysis, from his initial presentation with an ele-vated PSA level, when the primary treatments con-sidered included radical prostatectomy and inten-sive radiation treatment, to his current evaluation,when a decision about the use of chemotherapy hadto be made in the context of widespread disease.

Dr. Young, would you show us the slides of thespecimens from the initial prostate biopsy?

Dr. Robert H. Young

: Most of the cores were exten-sively involved by adenocarcinoma, even more ex-tensively on the left side than on the right side. Thepattern was not that of the usual small acinar adeno-carcinoma that is seen in 80 to 90 percent of prostatecancers, but rather a pattern of larger glands. Someareas were well differentiated and were classified asGleason grade 2, and some were Gleason grade 3C,with a cribriform pattern (Fig. 1A). Some cliniciansbelieve that Gleason grade 3 carcinomas with a crib-riform pattern have a somewhat worse prognosisthan Gleason grade 3 adenocarcinomas without acribriform pattern. In other areas, there were fusedsmall glands in a packed, microacinar pattern typi-cal of a Gleason grade 4 adenocarcinoma (Fig. 1B).The Gleason score, as opposed to grade, was 7 (thesum of the two highest grades, in this case 3 and 4).

management of localized prostate cancer

Dr. Kaufman

: At the time of his initial presentation,the patient appeared to have cancer localized to theprostate. The treatment options included radicalprostatectomy and radiation therapy. I would like toask Drs. McDougal and Shipley to discuss the rolesof radical prostatectomy and radiation therapy in thecurative treatment of this patient.

Radical Prostatectomy

Dr. W. Scott McDougal

: Radical prostatectomy has sev-eral advantages: examination of the specimen offers

discussion of management

Figure 1. Biopsy Specimens of the Prostate and a Paraaortic Lymph Node (Hematoxylin and Eosin Stains).

The initial, diagnostic biopsy specimen obtained contains extensive adenocarci-noma with several patterns (Panel A, 31). A large glandular pattern and a focal cribriform pattern, graded as Gleason 3C/5 was prominent, but there were also small fused glands (Gleason grade 4/5) (Panel B, 250), for a Gleason score of 7/10. The lymph-node biopsy specimen obtained at laparotomy (Panel C, 31) contains a large nodule (Gleason grade 4/5 adenocarcinoma) with a fused glan-dular pattern, similar to that seen in some areas of the prostate.

A B

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definitive knowledge of the pathological stage andgrade of the disease, and the patient benefits fromwhat I consider the most durable method of diseaseeradication over the long term. Patients may be strat-ified according to the pathological stage of their dis-ease. If the Gleason score is 2 to 4 and the clinicalstage is T1c (i.e., the patient has an elevated PSA lev-el without a palpable mass), the progression-freesurvival rate after a radical prostatectomy is approx-imately 90 percent; if the Gleason score is 5 to 6,the rate is about 80 percent; if the score is 7, the rateis about 55 percent; and if the score is 8 to 10, therate is less than 20 percent.

1

For patients who haveT2 disease, such as the patient under discussion, theprobability of 15 years of progression-free survivalis approximately 69 percent. The higher the Glea-son score, and the more extensive the disease, thegreater the likelihood of intraoperative and postop-erative complications. Intraoperative complicationsinclude bleeding and injury to the obturator nerve,the urethra, the rectum, or a major pelvic artery orvein. Postoperative complications may substantial-ly alter the patients quality of life; they fall intothree categories: incontinence, impotence, and ure-throvesical stricture.

The incidence of complications reported by pri-mary caregivers in single-institution studies tendsto reflect better results than the incidence reportedby investigators who are not the primary caregiversin large, multi-institution studies. The incidence ofurethrovesical stricture, for example, varies fromless than 1 percent to 9 percent. The incidence ofincontinence in single-institution studies is about8 percent, with 6 percent of the patients havingstress incontinence and 2 percent wearing morethan one pad a day. In assessments of incontinencein multi-institutional studies one year after the sur-gery, about one third of the patients are reported towear a pad.

2

Potency rates also vary, depending onwho asks the question of the patient, the age of thepatient, and the patients erectile status before theoperation. In studies in which the patients own as-sessment is used, potency rates vary from 90 percentin patients less than 50 years of age to 25 percent inthose greater than 70 years of age.

3

However, whenpatients are assessed with the use of appropriateoutcome measures by a disinterested third party inmulti-institutional studies, only 31 percent of pa-tients report that they have an erection and only9 percent report successful intercourse.

2

In a pop-ulation-based study of 1291 men who were evaluat-ed 18 or more months after radical prostatectomy,

8 percent were incontinent and 60 percent wereimpotent.

4

This patient was thus a good candidate for radi-cal prostatectomy, and at the age of 55 years, he hada low risk of side effects.

Radiation Therapy

Dr. William U. Shipley

(Radiation Oncology): The ad-vantages of external-beam radiation therapy as theprimary treatment for this patient with localizedprostate cancer are that it poses a very low risk ofurinary incontinence and stricture; it may eradicateextensions of the tumor beyond the capsule of theprostate; and when it is combined with hormonaltherapy, it may offer a chance of cure for some pa-tients, such as this one, with intermediate-risk tu-mors. The disadvantages of radiation therapy arethat the treatment is long, eight to nine weeks; athree-dimensional, conformal technique that al-lows the delivery of doses of at least 72 Gy may berequired; and the treatment adds a low risk of sub-sequent rectal symptoms. In addition, this thera-peutic method does not inform the clinician aboutpossible metastases to lymph nodes, and the long-term sequelae of ultrahigh-dose radiation treat-ments are not known.

The chance of recurrence-free survival after irra-diation, with the use of post-treatment PSA level asthe monitoring criterion, can be predicted by the

Figure 2. Bone Scans Obtained before and after Chemotherapy.

A scan obtained 7 years and 10 months after the diagnosis (Panel A) reveals metastatic lesions (arrows) in the lower thoracic and lumbar spine. Seven weeks after the initiation of chemotherapy (Panel B), the lesions show in-creased activity (arrows). This flare phenomenon results from an increase in osteoblastic activity in healing bone lesions

.

A B



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risk group of the patient at presentation. For pa-tients with low-risk tumors (stage T1c, a Gleasonscore of 6 or less, and a PSA level of 10 ng per milli-liter or less), the rate is 70 to 80 percent.

5

This pa-tient had an intermediate-risk tumor (stage T2 tu-mor, Gleason score 7, and an initial PSA level of 10to 20 ng per milliliter), and his expected chance ofsurvival would range from 50 to 55 percent if hewere given conventional external-beam radiationtherapy alone.

Over the past decade, the development of three-dimensional conformal therapy, which uses com-puter software to integrate CT images of the pa-

tients internal anatomy in the treatment position,has allowed the volume of tissue to which a highdose of radiation is delivered to conform more ex-actly to the shape of the tumor. This advance hasreduced the incidence of both early and late toxiceffects on normal tissue in patients with prostatecancer and allows higher cumulative doses to bedelivered with a reduced risk of late effects.

6,7

Thereis now evidence from both randomized and nonran-domized clinical trials of significant improvementin the rates of recurrence-free survival in patientswith intermediate-risk tumors when doses great-er than 70 Gy are used.

8-10

In addition, patients whohave intermediate-risk tumors have significantlyhigher disease-specific survival rates with a shortcourse of neoadjuvant androgen-suppression ther-apy and radiation treatment than they do with radi-ation treatment alone.

10

Thus, the current recommendation for this pa-

Figure 3. Axial CT Images of the Abdomen Obtained after the Intravenous Administration of Contrast Material.

A CT image obtained 7 years and 10 months after the di-agnosis reveals an enlarged lymph node close to the aor-tic bifurcation (Panel A, arrow). An image from a repeated CT scan obtained at the same level seven weeks after the initiation of chemotherapy shows diminution in the size of the pelvic lymph node (Panel B, arrow).

A

B

Figure 4. Axial CT Images of the Chest Obtainedafter the Intravenous Administration of Contrast Material.

An image obtained seven years and eight months after the diagnosis shows multiple nodules in both lungs (Panel A, arrows). An image obtained seven weeks after the initiation of chemotherapy shows a decrease in size and cavitation of some of the nodules (Panel B, arrows).

A

B



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tient would be irradiation to a total dose of 75 to76 Gy by the three-dimensional conformal tech-nique, preceded by a short course of neoadjuvantandrogen suppression. In recent reports, the ratesof disease progression 6 to 10 years after irradia-tion are similar to those in reports of series of pa-tients undergoing prostatectomy.

8,11

Strict contraindications to external-beam radia-tion therapy include prior pelvic irradiation, activeinflammatory bowel disease, a permanent Foleycatheter, and morbid obesity. For this patient, whohad none of these problems, radiation therapy is areasonable alternative to radical prostatectomy.

Dr. Kaufman

: Both radical prostatectomy andconformal external-beam radiation treatment cancure localized prostate cancer; cure is more likelyfor patients with low-risk disease than for patientsin the intermediate-risk and high-risk groups. Theincidence of serious incontinence after radical pros-tatectomy is about 5 percent when the procedure isperformed by experienced surgeons and virtuallynonexistent after radiation treatment; the rate of im-potence is about 50 percent after either treatment.Not surprisingly, surgeons prefer prostatectomyand radiation oncologists favor irradiation as thetreatment of choice.

12

No prospective comparativestudy of conformal external-beam radiation treat-ment with higher total doses of radiation and sur-gery has been reported.

After consultation with his physicians, this pa-tient chose to undergo radical prostatectomy. At lap-arotomy, enlarged pelvic lymph nodes were seen.Dr. Young, would you describe the specimens for us?

Dr. Young

:

On intraoperative gross examination,the three right obturator lymph nodes sampled wererubbery in texture and ranged from 0.5 to 2.0 cm ingreatest dimension; the single left obturator lymphnode was 1.4 cm in its greatest dimension and con-tained a nodule of firm, tan-to-white tissue, a find-ing indicating the presence of tumor. On micro-scopical examination of both frozen and permanentsections (Fig. 1C), the tumor had a small, acinar,fused glandular pattern similar to that seen in theprostate biopsy specimen. Two of the three lymphnodes on the right side and the one on the left sidecontained cancer.

management of locally advanced prostate cancer

Dr. Kaufman

: Dr. Gomery, you were the surgeon car-ing for this patient. Please tell us what you did andthe reasons for your decisions.

Dr. Pablo Gomery

(Urology): Because the biopsyhad revealed a rather poorly differentiated prostaticcarcinoma and examination of several lymph nodeshad shown grossly evident carcinoma, I believedthat the likelihood of a cure for this patient by pros-tatectomy was low and did not justify the potentialcomplications of the operation in a man of his agewho was sexually active, so I terminated the proce-dure without completing the prostatectomy.

Dr. Kaufman

: Dr. Zietman, what is the role of ra-diation treatment in this patient, who had positivenodes and in whom surgery was aborted?

Radiation Therapy

Dr. Anthony L. Zietman

: More than 90 percent of pa-tients who have node-positive prostate cancer haveoccult metastatic disease elsewhere. As a conse-quence, cure is unlikely with any localized therapy.Many patients, however, have bulky or aggressivedisease at the primary site, which may cause localsymptoms and may be the first site of tumor pro-gression. Two studies, one from the M.D. AndersonCancer Center

13

and one from this institution,

14

found that in patients treated with androgen depri-vation alone, the primary site was the most commonfirst site of progression, requiring subsequent lo-cal therapy in up to 73 percent of the patients. Incontrast, of the patients treated with both androgendeprivation and local therapy (radiation therapy ortransurethral prostatectomy), local recurrence ofdisease requiring therapy developed in 11 percentor less.

Local therapy plus androgen deprivation maytherefore be justified to extend the initial disease-free interval and to reduce symptomatic local pro-gression. In this patient, I recommended radiationtherapy; this was before the days of three-dimen-sional conformal treatment, and he received whatwas then our standard dose approximately 69 Gy.

Dr. McDougal

: The fact that you treated him lo-cally does not necessarily mean that you eradicatedthe local disease or eliminated the possibility of lo-cal progression.

Dr. Zietman

: Absolutely not.

Dr. Kaufman

: The patient did not experience anylocal side effects from the radiation therapy, and hestated that his sexual potency was unaffected. Hewas free of symptoms for seven years after the di-agnosis; then, while he was receiving flutamide,the PSA level rose to 0.9 ng per milliliter and thento 1.4 ng per milliliter. The flutamide was discon-tinued. Intramuscular leuprolide was begun six



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months later, but the PSA level continued to rise.A bone scan and chest and abdominal CT scanswere obtained four months later.

Dr. Mukesh G. Harisinghani

: The bone scan at thistime (Fig. 2A) shows areas of increased uptake inT10, the ribs bilaterally, and the right humerus.

Im-ages from a contrast-enhanced CT scan of the ab-domen and pelvis (Fig. 3A) show newly enlargedretroperitoneal lymph nodes adjacent to the upperand lower abdominal aorta and the bifurcation a finding that probably represents metastatic dis-ease. The lung windows from the chest CT scan(Fig. 4A) show multiple nodules in both lungs, andthe mediastinal windows show enlarged precarinaland subcarinal lymph nodes; all of these findingsalmost certainly represent metastatic disease.

Dr. Kaufman

: What are the treatment options atthis point? The patient has been receiving leuprolidefor four months, with no improvement. Dr. Smith,would you discuss hormone treatment for advancedprostate cancer?

Hormonal Therapy

Dr. Matthew R. Smith

(Hematology/Oncology): An-drogen-deprivation therapy by either bilateral or-chiectomy or administration of a gonadotropin-releasing hormone agonist such as leuprolide isthe mainstay of treatment for advanced or metastat-ic prostate cancer. Androgen-deprivation therapy byeither method decreases serum testosterone levelsby more than 95 percent and leads to objective re-sponses in the majority of patients. Monotherapywith antiandrogens is an alternative to standard an-drogen-deprivation therapy. Flutamide is a nonste-roidal antiandrogen that blocks the action of testos-terone by binding to the androgen receptor in targettissue. This mans disease responded to flutamidemonotherapy for more than six years. About twothirds of men with progressive disease who receiveantiandrogen monotherapy will respond to subse-quent androgen-deprivation therapy. The long du-ration of the response to flutamide monotherapy inthis case suggests a higher-than-average chance ofa response to subsequent medical or surgical cas-tration. In addition, in a few men treated with agonadotropin-releasing hormone agonist, testos-terone levels approaching those achieved by bilat-eral orchiectomy are not reached. I recommend themeasurement of serum-testosterone levels for pa-tients who either do not have a response or who haveunexpectedly short responses to a gonadotropin-releasing hormone agonist. Bilateral orchiectomymay prove effective in the men whose testosterone

production cannot be adequately suppressed with agonadotropin-releasing hormone agonist.

Dr. Kaufman

: Given the patients progression ofdisease while he was receiving hormonal treat-ment, we considered multiagent chemotherapy.Dr. Michaelson, would you discuss the role of che-motherapy in the treatment of a patient, such as thisone, who has advanced, hormone-refractory pros-tate cancer?

Chemotherapy

Dr. M. Dror Michaelson

(Hematology/Oncology): Theearly experience with cytotoxic chemotherapy inprostate cancer was largely unsuccessful, and untilthe 1990s, chemotherapy was not considered a stan-dard treatment for this disease. Two randomized,phase 3 studies in the mid-1990s showed a benefitwith mitoxantrone and corticosteroids as comparedwith corticosteroids alone, with improvement in thepatients scores on pain scales and in their overallquality of life.

15,16

However, even this combinationproduced a decrease in the PSA level in only 30 to 35percent of the patients. The same studies also failedto show a benefit in overall or disease-specific sur-vival among patients treated with mitoxantrone andcorticosteroids as compared with those treated withcorticosteroids alone.

Taxane-based regimens have now been studiedin numerous phase 1 and 2 clinical trials, and theyappear to be more promising than previously stud-ied therapies. Paclitaxel and docetaxel alone or incombination with estramustine, with or without car-boplatin and etoposide, have been studied in multi-ple phase 1 and 2 trials. Many of these trials havedocumented response rates in excess of 50 per-cent.

17,18

In response to these data, an Intergroupphase 3 study comparing docetaxel and estramus-tine with the current standard therapy, mitoxan-trone plus corticosteroids, is under way.

In the past few years, clinical trials have evaluatedthe usefulness of adding a third agent to the combi-nation of docetaxel and estramustine. These haveincluded biologic agents targeted against growth-factor pathways and traditional cytotoxic chemo-therapy drugs. At this hospital, my colleagues andI have conducted a study of a regimen that combinesdocetaxel, estramustine, and carboplatin in menwith hormone-refractory prostate cancer. Accrual tothis study has been completed, but the results arenot yet available. The patient under discussion wasenrolled in this trial.

Dr. Kaufman

: Eight years after the initial diagno-sis, chemotherapy consisting of docetaxel, estra-



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mustine, and carboplatin was initiated, carried outfor six cycles, and completed in six months. Duringthe six months of chemotherapy, the patient had vir-tually no symptoms except for very mild fatigue. Hedid not miss work and was able to continue his activ-ity of mountain climbing. His PSA level dropped to0.5 ng per milliliter shortly after the start of chemo-therapy, and at the completion of chemotherapy hisPSA level was less than 0.2 ng per milliliter.

Dr. Harisinghani, would you show us the imagesthat were obtained after the treatment?

Dr. Harisinghani

: On the bone scan obtained sevenweeks after the start of chemotherapy (Fig. 2B), thepreexisting lesions all showed increased activity.This phenomenon, which has been called a flare,represents increased osteoblastic activity within themetastases, which is a sign of improvement aftertreatment. No new lesions were identified. Theparaaortic lymphadenopathy has regressed in sizeas compared with that seen on the previous abdom-inal CT scan (Fig. 3B). A chest CT scan obtained atthe same time reveals that the pulmonary noduleshave regressed in size (Fig. 4B) and show some cav-itation, indicating a response to therapy. The medi-astinal nodes have all decreased in size.

Dr. Kaufman

: These images illustrate an impor-tant point. When the patients chest and abdominalCT scans showed that there had been dramatic im-provement, the bone scan was initially read as re-vealing an increase in metastatic disease. On review,however, it became clear that this finding was a flarereaction all of the increased uptake was in areasthat had previously been involved by tumor. This isa rare phenomenon that occurs as a result of treat-ment, and it is important to recognize.

Unfortunately, four months after the completionof chemotherapy, the patients PSA level began torise, and three months later nine years after theinitial diagnosis and one year after the initiation ofchemotherapy it was 6.3 ng per milliliter. Re-peated CT scans revealed stable lung nodules. Anabdominopelvic CT scan showed an increase in thesize of the left paraaortic lymph nodes. A bone scanshowed a new lesion in the T9 vertebral body and alesion in T10 that

had increased in size.Because of his good response and because he did

not have a toxic reaction to the chemotherapy regi-men, we decided to treat him again, using the sameagents. At the time of the first chemotherapy visit,he reported smoky vision in his left eye, with no gaitdisturbance or headaches. He was evaluated by a

vitreoretinal specialist, who conducted fluoresceintesting, indocyanine green angiography, and opticalcoherence tomography; a 1-mm area of thickeningwas observed, a finding consistent with a single cho-roidal metastatic lesion on the left retina. After onecycle of chemotherapy, the patient noted an im-provement in visual clarity. His PSA level decreasedfrom 6.0 to 3.0 ng per milliliter after the first cycleof chemotherapy; after seven cycles, his PSA levelwas less than 0.2 ng per milliliter.

Dr. Alex F. Althausen

(Urology): What is the aver-age duration of tumor-free survival for a patient whopresents with known nodal disease and is given allthese therapies? Is this patients course unusual inbeing protracted over nine years? Or, can we tell pa-tients that even if the results of an MRI or CT scanare positive for cancer, with appropriate chemother-apy they can expect nine or more years of a reason-able quality of life?

Dr. James Talcott

(Medical Oncology): This pa-tients long survival is unusual, but the course ofprostate cancer is highly variable, even after adjust-ments for tumor stage, Gleason score, and PSA lev-el. Earlier diagnosis as a result of PSA screeninghas led to a longer survival for all patients, throughstage migration.

19

In a small, randomized trial ofimmediate hormone treatment as compared withtreatment at the time of clinical relapse in patients,such as this man, with positive nodes, survival wasimproved in the immediate-treatment group,

20

butgrowing evidence of toxicity from long-term andro-gen-deprivation therapy suggests that discussionshould precede chemical castration of asymptom-atic men without metastases.

21

Dr. Kaufman

: At the most recent follow-up, thepatients PSA level was 0.2 ng per milliliter. A bonescan and abdominal, pelvic, and chest CT scans allshowed stable disease. Unfortunately, his eye lesionrecently recurred, and he is now receiving proton-beam therapy to the eye. In the care of this patientover what is now a 10-year span, we have used al-most every known treatment for prostate cancer. Re-markably, the patient has felt well throughout theentire course of his illness, carrying on with his nor-mal occupation and activities.

Adenocarcinoma of the prostate with metastases.

anatomical diagnosis



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references

1.

Hull GW, Rabbani F, Abbus F, WheelerTM, Kattan MW, Scardino PT. Cancer con-trol with radical prostatectomy alone in1,000 consecutive patients. J Urol 2002;167:528-34.

2.

Talcott JA, Rieker P, Clark JA, et al. Pa-tient-reported symptoms after primary ther-apy for early prostate cancer: results of aprospective cohort study. J Clin Oncol 1998;16:275-83.

3.

Quinlan DM, Epstein JI, Carter BS,Walsh PC. Sexual function following radicalprostatectomy: influence of preservation ofneurovascular bundles. J Urol 1991;145:998-1002.

4.

Stanford JL, Feng Z, Hamilton AS, et al.Urinary and sexual function after radicalprostatectomy for clinically localized pros-tate cancer: the Prostate Cancer OutcomesStudy. JAMA 2000;283:354-60.

5.

Shipley WU, Thames HD, Sandler HM,et al. Radiation therapy for clinically local-ized prostate cancer: a multi-institutionalpooled analysis. JAMA 1999;281:1598-604.

6.

Michalski JM, Purdy JA, Winter K, et al.Preliminary report of toxicity following 3Dradiation therapy for prostate cancer on3DOG/RTOG 9406. Int J Radiat Oncol BiolPhys 2000;46:391-402.

7.

Hanlon AL, Watkins Bruner D, Peter R,Hanks GE. Quality of life study in prostatecancer patients treated with three-dimen-sional conformal radiation therapy: com-paring late bowel and bladder quality of lifesymptoms to that of the normal population.Int J Radiat Oncol Biol Phys 2001;49:51-9.

8.

Kuban DA, Thomas HD, Levy LB, et al.

Long-term multi-institutional analysis ofstage T1-T2 prostate cancer treated with ra-diotherapy in the PSA era. Int J Radiat OncolBiol Phys 2003;57:915-28.

9.

Pollack A, Zagars GK, Smith LG, et al.Preliminary results of a randomized radio-therapy dose-escalation study comparing 70Gy with 78 Gy for prostate cancer. J Clin On-col 2000;18:3904-11.

10.

Pilepich MV, Winter K, John MJ, et al.Phase III Radiation Therapy OncologyGroup (RTOG) trial 86-10 of androgen dep-rivation adjuvant to radiotherapy in locallyadvanced carcinoma of the prostate. Int JRadiat Oncol Biol Phys 2001;50:1243-52.

11.

Yock TI, Zietman AL, Shipley WU,Thakral HK, Coen JJ. Long-term durabilityof PSA failure-free survival after radiothera-py for localized prostate cancer. Int J RadiatOncol Biol Phys 2002;54:420-6.

12.

Fowler FJ Jr, McNaughton Collins M, Al-bertsen PC, Zietman AL, Elliott DB, BarryMJ. Comparison of recommendations byurologists and radiation oncologists fortreatment of clinically localized prostatecancer. JAMA 2000;283:3217-22.

13.

Sands ME, Pollack A, Zagars GK. Influ-ence of radiotherapy on node-positive pros-tate cancer treated with androgen ablation.Int J Radiat Oncol Biol Phys 1995;31:13-9.

14.

Morris AD, Zietman AL, Althausen AF,Kaufman DS, Shipley WU. The value of ex-ternal beam radiation in node positive pros-tate cancer. Urol Oncol 2001;6:255-60.

15.

Kantoff PW, Halabi S, Conaway M, et al.Hydrocortisone with or without mitoxan-trone in men with hormone-refractory pros-

tate cancer: results of the Cancer and Leuke-mia Group B 9182 study. J Clin Oncol 1999;17:2506-13.

16.

Tannock IF, Osoba D, Stockler MR, et al.Chemotherapy with mitoxantrone plusprednisone or prednisone alone for sympto-matic hormone-resistant prostate cancer: aCanadian randomized trial with palliativeend points. J Clin Oncol 1996;14:1756-64.

17.

Hudes GR, Nathan F, Khater C, et al.Phase II trial of 96-hour paclitaxel plus oralestramustine phosphate in metastatic hor-mone-refractory prostate cancer. J Clin On-col 1997;15:3156-63.

18.

Petrylak DP, Macarthur RB, OConnor J,et al. Phase I trial of docetaxel with estra-mustine in androgen-independent prostatecancer. J Clin Oncol 1999;17:958-67.

19.

Feinstein AR, Sosin DM, Wells CK. TheWill Rogers phenomenon: stage migrationand new diagnostic techniques as a sourceof misleading statistics for survival in can-cer. N Engl J Med 1985;312:1604-8.

20.

Messing EM, Manola J, Sarosdy M,Wilding G, Crawford ED, Trump D. Imme-diate hormonal therapy compared with ob-servation after radical prostatectomy andpelvic lymphadenectomy in men with node-positive prostate cancer. N Engl J Med 1999;341:1781-8.

21.

Smith MR. Osteoporosis and other ad-verse body composition changes during an-drogen deprivation therapy for prostate can-cer. Cancer Metastasis Rev 2002;21:159-66.

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Documents

Case 21-2004 a 63-Year-Old Man Castration